Originally Published IVD Technology November/December 2005
INDUSTRY NEWS
Third Wave pharmacogenetic test cleared by FDAThe promise of mainstream personalized medicine moved one step closer to reality with FDA's approval of the Invader UGT1A1 molecular assay by Third Wave Technologies Inc. (Madison, WI) in August. It is the first pharmacogenetic test to be cleared for use as a companion diagnostic to a specific drug. The Invader assay is used to identify patients who could experience adverse reactions to Camptosar (irinotecan), a colorectal chemotherapy drug manufactured by Pfizer Inc. The test detects mutations in the UGT1A1 gene, which produces a drug-metabolizing enzyme.
"FDA sees the Invader as a promising development in the shift toward personalized medicine and the use of genomic testing for better decision making in the selection and dosing of drugs. FDA used many of the tools in its flexible regulatory toolbox to bring this test to market in a timely and least-burdensome manner," says Steven Gutman, MD, director of the Office of In Vitro Diagnostic Device Evaluation and Safety. "Both the Center for Drug Evaluation and Research (CDER) and the Center for Devices and Radiological Health (CDRH) have been working hard on guidance development and educational programming to promote rapid transfer of this new technology from the research bench to the bedside."
According to some industry experts, the approval is significant both for the development of personalized medicine as well as for the evolution of Third Wave as an IVD manufacturer. "[This clearance] signals that FDA will support efforts in this direction and should encourage other companies to follow suit," says Richard Schifreen, PhD, vice president, research products, at Mirus Bio Corp. (Madison, WI). Schifreen also points out that the Invader assay is the company's first FDA-approved test. "Turning the corner from analyte specific reagents to Class II IVDs is a big step that demonstrates Third Wave's commitment to becoming a significant diagnostic company. It will be interesting to see if and when they are able to tackle a Class III premarket approval for a diagnostic assay such as human papilloma virus," he says.
Rod Hise, vice president of corporate affairs at Third Wave, says that FDA sent strong signals to the company about its support for the test. "FDA's accelerated clearance of our UGT1A1 test—after it asked Third Wave to develop the test—is a sign of how seriously the agency is encouraging the development and use of pharmacogenetic tests," he says.
After considering whether to pursue a de novo classification for the assay, Third Wave decided to submit a traditional 510(k) application, using the AmpliChip produced by Roche Molecular Systems Inc. (Pleasanton, CA) as the predicate device. The company is currently working to develop an assay to detect the risk of adverse reaction to the anticoagulant Coumadin (warfarin). According to Hise, FDA has indicated that Coumadin might be the next candidate for relabeling with dosing recommendations based on a patient's genetic profile.
The approval of the Invader UGT1A1 comes after indications from FDA this year that it is taking a serious look at the capabilities of gene-based technologies. This spring, it released a final guidance on pharmacogenomic data submissions. Shortly after, it distributed a preliminary concept paper on drug-diagnostic development.
"Both drug and diagnostic companies are beginning to appreciate the potential benefits of genomic testing," says Gutman. "Both the CDER voluntary genomic data submission process and the CDRH preinvestigational device exemption process are being used to introduce FDA to a wide variety of potential future products for use in making personalized medical choices."
Although Third Wave developed and sought approval for UGT1A1 test separate from Pfizer, Hise agrees that FDA's ideas on codevelopment show a willingness to work with industry. "The concept paper is one of several strong signals FDA has sent recently about its view of the increasing importance of pharmacogenetics," he says. Still, the ultimate success of drug-diagnostic codevelopment may rest with the pharmaceutical industry's perception of genetic tests. "I think that pharmaceutical companies have accepted the value of companion diagnostics for oncology drugs, especially monoclonal antibodies," says Schifreen. "I don't think they have embraced the concept in other therapeutic areas—at least not yet."
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